PH1125 - Receptors

Question 1

what is a receptor?

Answer 1

• protein macromolecule which is a recognition site normally activated by neurotransmitters. hormones or drugs

Question 2

what are channel receptors? (3)

Answer 2

• hole in membrane
• allows passage of ions through membrane
• activation of conductance

Question 3

what are g protein receptors? (3)

Answer 3

• receptor couples with g protein
• generates second messenger
• activation of signal in cell

Question 4

what are enzyme receptors? (3)

Answer 4

• activation of enzyme that sits in membrane
• phosphorylation of key components in cell
• activation of cell signalling

Question 5

what is a ligand?

Answer 5

• substance that interacts with a biomolecule to serve a biological purpose

Question 6

what are examples of intermolecular forces? (4)

Answer 6

• electrostatic forces
• H bonding
• van der waals
• hydrophobic interactions

Question 7

what is the intrinsic efficacy?

Answer 7

• ability of an agonist to alter receptor conformation to elicit a response

Question 8

what is the maximum response?

Answer 8

• full occupation o receptors

- dose increase gives no bigger response

Question 9

what is the threshold dose?

Answer 9

• sufficient receptors occupied to elicit a response

Question 10

what is an agonist?

Answer 10

• a molecule capable of binding to and activating a receptor

Question 11

what is a competitive antagonist? (2)

Answer 11

• receptor antagonist that binds to a receptor but does not activate the receptor
• will compete with available agonist for receptor binding sites on the same receptor

Question 12

what is affinity?

Answer 12

• measure of how avidly the agonist (drug) binds to the receptor

Question 13

what way does the curve shift with higher affinity agonist and agonist and why? (2)

Answer 13

• agonist curve shifts left

- binds to the receptor better therefore lower concentration required to elicit the same response

Question 14

what way does the curve shift with lower affinity agonist and agonist and why? (2)

Answer 14

• agonist curve shifts right
• doesn’t bind as well to the receptor therefore a higher concentration is needed to elicit the same response as a higher affinity agonist

Question 15

what is efficacy?

Answer 15

• relationship between receptor occupancy and the ability to initiate a response at the molecular, cellular, tissue or system level

Question 16

what way does the curve shift with an agonist and an agonist with competitive antagonists and why? (3)

Answer 16

• agonist curve shifts right
• competitive antagonist sits and blocks the receptors
• agonist concentration needs to be increased

Question 17

what is a functional non-competitive antagonist?

Answer 17

• second messenger pathway blocked by antagonist

Question 18

what is an allosteric antagonist?

Answer 18

• drug that modulates the response of an antagonist but makes the receptor less effective

Question 19

what way does the curve shift with an agonist and an agonist with irreversible antagonists (high dose) and why? (3)

Answer 19

• agonist curve shifts right and maximum tissue response decreases
• an irreversible antagonist reduces the pool of receptors
• blocked receptors results in reduced effect

Question 20

what is the relationship between a full agonist and partial agonist when they compete?

Answer 20

• the partial agonist acts like a competitive antagonist

Question 21

what are spare receptors?

Answer 21

• present in a system when full agonist produces a maximum response when only a fraction of the total receptor population is occupied

Question 22

what is ec50 in term of occupancy and response? (2)

Answer 22

• 50% occupancy

- 50% response

Question 23

D + R ⇌ DR

Ka and Kd?

Answer 23

• d is the concentration
• r is the receptor
• dr is the drug-receptor compex
• Ka (association constant) is the forward reaction
• Kd (disassociation constant) is the backward reaction

Question 24

what is Ka? (2)

Answer 24

• high affinity vs low affinity

- BIG number

Question 25

what is Kd? (2)

Answer 25

• related to concentration

- SMALL number

Question 26

what is the equation for Ka in terms of Kd?

Answer 26

• Ka = 1/Kd

Question 27

what are the Ka and Kd values useful for?

Answer 27

• useful for estimating how much drug to use and estimating relative selectivity

Question 28

what is the schild equation?

Answer 28

• log (rose ratio - 1) = log [antagonist] - log (Kd)

- y = mx + c

Question 29

for a competitive antagonist what is the gradient on a schild plot?

Answer 29

-1

Question 30

what can cause a schild plot to differ from 1? (4)

Answer 30

• non-competitive antagonism; antagonist interacts with the receptor at non-overlapping site)
• drug disposition mechanism / other non-equilibrium steady state present
• competitive antagonism of a heterogeneous receptor population subserving the same response
• multiple drug effects occur